AppropriationsUpdate from Capitol HillBy Brandon Leonard, MA

The 116th Congress began
Jan. 3 with unfinished business from 2018, many new faces, and a new
political dynamic now that the Democrats have a majority in the House and the
Republicans have maintained a majority in the Senate.

The 115th Congress passed
five out of the 12 Fiscal Year (FY) 2019 spending bills on time, including the Labor–Health
and Human Services (HHS) – Education bill. As part of this bill, the National
Institutes of Health (NIH) received a $2 billion increase in funding for FY19. However, congressional leaders and the White House were unable to reach an agreement on
the remaining FY 2019 spending bills before a Dec. 21 deadline. Due to the
impasse, funding expired for the departments of Housing and Urban Development,
Transportation, Agriculture, Homeland Security, Commerce, State, Justice,
Interior and Treasury, as well as agencies including the Food and Drug
Administration (FDA) and the National Science Foundation (NSF).

The 116th Congress will
prioritize an agreement to re-open the affected agencies. The AACR has strongly
advocated for funding for the FDA, and particularly for the FDA’s Oncology
Center of Excellence (OCE). Funding for the FDA and OCE remain in limbo and the
FDA cannot accept new product applications until an agreement is reached to
finalize the FY19 appropriations.

Meanwhile, the FY 2020
appropriations process is already underway as federal agencies prepare their
budgets. President Trump is expected to release his budget proposal in
February. He has proposed significant cuts to domestic spending during each of
his years in office, though Congress has rebuffed those efforts and in many
cases, has provided significant increases for agencies which were targeted for
cuts by the White House. For FY 2020, the president has asked his cabinet
secretaries to each cut five percent from their budget.

One of the most important
actions for the new Congress will be reaching a budget agreement to lift strict
caps on both defense and nondefense spending as required under the Budget
Control Act. If Congress wants to continue to increase funding for priority
areas like the NIH next year, a bipartisan budget agreement followed by a
larger allocation for appropriations bills, including the Labor, HHS and
Education bill, is required.

In the opening weeks of the new year, the AACR will be meeting with new
members of Congress as well as returning members who play a key role in appropriations
and health policy. We will urge Congress and the White House to reach a
bipartisan budget agreement, and will continue to make the case to Congress
that robust, sustained, and predictable funding increases for the NIH are
essential to the health and economic security of our country.

On Dec. 18, 2018, U.S. Surgeon General, Jerome Adams, MD, MPH, issued an advisory on youth electronic cigarette (e-cigarette) use. In the advisory, the surgeon general said parents, teachers, health professionals, and government officials must take "aggressive steps" to keep children from using e-cigarettes. The surgeon general's advisory notes that the popular Juul e-cigarette cartridge contains as much nicotine as a pack of cigarettes. Additionally, Dr. Adams stated that Juul's liquid nicotine mixture is specially formulated to give a smoother, more potent nicotine buzz. The advisory is also calling for new local restrictions including taxes and indoor vaping bans.

The advisory was issued the day after data from National Institutes of Health's (NIH) Monitoring the Future survey showed that America's teens reported a dramatic increase in their use of e-cigarettes in just a single year, with 37.3 percent of 12th graders reporting use in the past 12 months, compared to 27.8 percent in 2017. The data from the NIH survey mirrored the U.S. Food and Drug Administration's (FDA) 2018 National Youth Tobacco Survey which showed that youth use of e-cigarettes has surged to epidemic proportions in the U.S. The number of high school students who use e-cigarettes has risen 78 percent last year to about 3.6 million, or 20 percent of high school students. Use among middle school students has increased about 48 percent. Due to these alarming statistics, many public health officials are worried that we are at risk of addicting another generation to the harmful effects associated with nicotine. In addition to the U.S. Surgeon General's advisory, the FDA Commissioner, Scott Gottlieb, MD, has stated that any innovations that could present an alternative to smoking, such as e-cigarettes, cannot come at the expense of addicting a generation of children to nicotine through these same delivery vehicles.

The AACR has been very active on this issue. On July 18, 2018, the AACR hosted a congressional briefing titled "E-cigarettes: Striking a Balance Between Preventing Youth Nicotine Addiction and Helping Current Smokers Quit Combustible Cigarettes." The panelists presented the latest available science pertaining to the effects and content of e-cigarettes and suggested approaches to halting the concerning rise in youth vaping and nicotine addiction. The AACR will continue to monitor both agency (i.e. FDA, CDC, and NIH) and congressional action on e-cigarettes in the new year.

FDA RecognizesGenetic Variant Database
By Trevan Locke, PhD

For the first time, the U.S. Food and Drug Administration (FDA) has recognized a public database containing information about genetic variants and how they relate to a disease. The Clinical Genome Resource (ClinGen) Consortium ClinGen Expert Curated Human Genetic Data, a database of germline variants funded by the National Institutes of Health, can now serve as a recognized source of valid scientific evidence to support clinical validity in premarket submissions to the agency. This recognition will allow test developers to use information in the database to support test validity rather than having to generate that data on their own.

This recognition pathway is based on Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics, guidance released by the FDA in April 2018. This guidance seeks to encourage data sharing and outlines how developers can use evidence from recognized publicly-accessible databases to support claims of clinical validity. A genetic test is clinically valid if the variant it is testing for has a meaningful relationship to a specific disease (such as confirming presence of a disease, or as an indicator of treatment efficacy). In addition to providing the FDA-recognition pathway used here for ClinGen, this guidance outlines recommendations for data transparency, quality, validation, curation, and privacy that database administrators can use to help demonstrate that a database can be used as valid scientific evidence.

The AACR has carefully monitored the development of this guidance, and submitted comments on the 2016 draft. In finalizing the guidance, the FDA clarified the definition of "publicly-accessible" further explaining that the best practice for such databases is an open access model but that databases that charge fees for commercial use may also fall under this guidance. The final guidance also provided additional information based on feedback on the draft including guidelines for choosing specific reporting nomenclature, expanding the guidance section on metadata to provide additional information about characteristics of high quality data to inform analytical purpose, and describing the agency's planned annual review process for recognized databases.

"With our policies, we've sought to create an efficient regulatory pathway that promotes the more rapid development of important tests that can transform medical care while assuring their accuracy and clinical relevance. Our continued efforts, including today's recognition, will advance this process and help patients gain access to more sophisticated tests that provide important genetic information, allowing for more targeted medical care," said Commissioner Scott Gottlieb, MD.

As other databases, including those of somatic variants, pursue and gain such FDA recognition, test developers will have valuable resources to draw from to aid their development processes.

FDA ReleasesFramework for Use of Real-world Evidence
By Trevan Locke, PhD

In December, the U.S. Food and Drug Administration (FDA) released a Framework for FDA's Real-World Evidence Program. The framework is intended to aid in the evaluation of potential uses of real-world evidence (RWE) to help support supplemental applications for a drug or biologic already approved by the FDA or to satisfy post-market requirements for an approved drug. RWE is the clinical evidence about the usage and potential benefits or risks of therapeutics derived from real-world data (RWD). RWD are data relating to patient health or the delivery of health care. RWD can come from a variety of sources including medical claims data, electronic health records, patient-reported outcomes, and product or disease registry data.

The framework, mandated by the 21st Century Cures Act, is the latest FDA effort to explore the use of RWE. The Center for Devices and Radiologic Health has routinely used RWE to evaluate medical devices, using sources such as patient registries and electronic health records to support over 50 regulatory decisions. Outside of the device space, the agency is also experienced with RWE to supplement traditional clinical trials and to monitor and evaluate the safety of drug products. For the latter, Sentinel, the FDA's electronic system for securely accessing information from RWD sources, has been used extensively for over a decade to monitor the safety of medical products. However, RWE has only been used as primary support for product approval in limited cases, such as the initial accelerated approval of blinatumomab. That approval was based on the comparison of a single treatment arm to an external control arm made up of historical data from 694 comparable patients.

With this framework, the agency plans to explore how RWE can be further used as support for approvals by considering the following, both in the context of evaluating appropriate supplemental applications and as a general guide for RWE development efforts across the agency:

Whether the RWD are fit for use;

Whether the trial or study design used to generate RWE can provide scientific evidence to answer or help answer the regulatory question; and

To support this approach, the FDA will consider updating or releasing guidance documents on topics related to RWE including: assessing the reliability of RWD, addressing potential gaps in RWD sources, considerations for clinical trials that include RWE elements, and on observational studies using RWD. Additionally, the FDA plans to seek out collaboration opportunities with stakeholders interested in RWE.

"This is a top strategic priority for the FDA. We're committed to realizing the full potential of these tools in advancing the development of novel therapeutic products and strengthening our regulatory oversight of medical products across the life-cycle continuum," said FDA Commissioner Scott Gottlieb, MD.

The recent hire of Amy Abernethy, MD, PhD, as the principal deputy commissioner of food and drugs, is further proof that the commissioner and the agency are making RWE a high priority. Abernethy will be leaving her role as chief medical officer, chief scientific officer, and senior vice president for oncology at Flatiron Health, an electronic health records company focused on cancer. Her work there has centered on the use of RWE to aid in the development of cancer therapeutics. Prior to her work at Flatiron, Abernethy served as director of the Duke Cancer Care Research Program. The AACR Office of Science Policy and Government Affairs looks forward to continued collaboration with Dr. Abernethy and the FDA, as we work together to advance safe and effective cancer therapies for patients.

The U.S. Food and Drug Administration (FDA) is planning significant updates to both major medical device approval pathways. Most device approvals utilize the 510(k) pathway, which is applied to low-to-moderate risk devices that are considered substantially equivalent to existing approved devices, referred to as predicate devices. The De Novo pathway is used for novel, low-to-moderate risk devices for which there are no existing devices on which to base substantial equivalence. In this pathway, performance of the device is evaluated independently of existing devices that may have the same function but different mechanisms of action.

In November 2018, FDA announced steps it hopes to take to modernize the 510(k) program. These changes are intended to push device manufacturers to use newer predicate devices or objective performance criteria as comparators when seeking approval for new medical devices. The vast majority—82 percent in 2017—of device approvals utilize the 510(k) pathway, but nearly 20 percent of those rely on predicates older than 10 years. The use of outdated predicates could hinder adoption of the most recent technological advances, performance standards, and risk/benefit analyses, thereby limiting progress in device development.

Therefore, FDA is proposing to list on its website devices that were cleared using predicates that are more than 10 years old. The goals of this action are to increase awareness around the identity of these products and, hopefully, motivate sponsors and physicians to make use of the most modern technologies and current advances in the development and use, respectively, of medical devices. FDA is also considering sunsetting some older predicates, a move that may require congressional action. Additionally, in 2019, FDA intends to finalize guidance proposed in April 2018 to expand use of the Abbreviated 510(k) program, by which sponsors of certain "well-understood" device types can demonstrate safety and effectiveness of new devices through the use of performance criteria rather than through comparison to predicates.

As another way to promote the use of more modern predicates, FDA announced in December 2018 a proposed rule to establish procedures and criteria for the De Novo classification process. The proposed regulations would provide structure, clarity, and transparency to the De Novo pathway for developers and reviewers alike. Among the provisions laid out in the proposed rule are: criteria for submitting De Novo requests; the format and content of requests; device classification criteria; and procedures for accepting, reviewing, withdrawing, and granting (or declining) requests.

By increasing efficiency in the classification process, FDA expects more developers will take advantage of the pathway, thereby establishing more devices that can serve as modern predicates. FDA's ultimate goal for all of these steps is to improve patient care and outcomes by ensuring new devices reflect modern technology and standards.

Savethe Date for the 2019 AACR-AACI Hill Day

The AACR and the Association of American Cancer Institutes (AACI) invite you to Capitol Hill Tuesday, April 30, 2019. This Hill Day will bring cancer center directors, researchers, physician-scientists, cancer survivors and other advocates to Capitol Hill to build support for a strong federal investment in cancer research and biomedical research. Stay tuned for more information and registration details.